Although the beneficial effects of natural and semi-synthetic corticosteroids in the treatment of inflammatory and allergic conditions have been appreciated for over 30 years, complications arising from steroid therapy have imposed limitations on the clinical use of this class of drugs. The shortcomings are largely inherent in the nature of corticosteroids themselves; not only do glucocorticosteroids possess multiple biological activities, but the structural requirements for various activities appear to be overlapping and inseparable. If the actions of corticosteroids could be localized many of the complications could be eliminated. Although methods for the local administration of steroids have been devised complications associated with local steroid treatment for psoriatic, rheumatologic, eczematous, asthmatic, and ophthalmic patients have been reported. This situation calls for new approaches in developing anti-inflammatory steroids that are devoid of toxicities.
In developing this invention several considerations were kept in mind: (i) corticosteroid pharmacotherapy appears to offer an abundance of agents, but no truly safe drug: (ii) systemic effects of steroids are unnecessary complications which accompany treatment of many inflammatory conditions; (iii) an intact ketol side chain is not an absolute requirement for the anti-inflammatory activity of corticosteroids and (iv) steroid acid esters with intact ring structures corresponding to the known potent glucocorticoids retain anti-inflammatory activity but upon entry into the circulatory system from the site of administration are hydrolyzed to steroid acids that are inactive and readily excreted.
Now it has been found that ester derivatives of steroid-20.alpha.-ol-21-oic acid, steroid-20.beta.-ol-21-oic acid, and certain proportionate mixtures thereof applied locally, possess anti-inflammatory activity but do not suppress adrenal function or liver glycogen content in rats.